We have discovered a paradoxical increase in glucagon in response to elevated glucose levels in ventromedial hypothalamic type lesioned weanling rats. The paradox persists when islets from these are perifused with 300 micrograms percent glucose. Morphologically the islets show hyperplasia with two to several having grown together. Lesioned animals also have a diminished insulin response to aminogenic stimulation and a slightly augmented glucagon response in vivo and in vitro in isolated perifused islets. These observations are very similar to islet morphology and A-cell changes reported in genetic diabetic ob/ob mouse and in human adult onset diabetes.